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Research Programs: Reproductive Toxicology

Main Faculty: D.N. Rao Veeramachaneni

The major efforts in reproductive toxicology at ARBL focus mainly on the male. Several recent reports indicate deteriorating trends in optimal reproduction in the human male particularly in the industrialized world. Common pollutants having hormone-mimicking capabilities have been implicated in these phenomena. To circumscribe cause-and-effect paradigms associated with these situations, the Veeramachaneni laboratory has been investigating the developmental as well as long-term reproductive sequelae of perinatal exposure to ubiquitous pollutants utilizing mammalian and amphibian animal models.

The overall objective of this pursuit is to address if the widely perceived concern -- global decline in seminal quality and reproductive health -- is really idiopathic, as male infertility often is labeled, or a consequence of exposure to environmental pollutants. The compounds that are being studied include anti-androgenic pesticides (DDT and its metabolites; vinclozolin), water disinfection byproducts (dibromoacetic acid, bromochloroacetic acid), detergents (alkyl phenols), and plasticizers (phthalates). Typically rabbits are used as an animal model because of their relatively long infantile phase of reproductive development (a vulnerable window for toxicant exposure), which approximates that of humans and farm animals.

Some of the tested chemicals caused lasting effects on spermatogenesis and sexual function. For example, following in utero and lactational exposure to vinclozolin, acrosomal dysgenesis and demasculinized sexual behavior was observed as adults. We found that prenatal exposure to vinclozolin disrupts selective aspects of the gonadotropin-releasing hormone neuronal system of the rabbit.

This laboratory has also found that developmental exposures of rabbits to some of these chemicals cause cryptorchidism and abnormal differentiation of germ cells into carcinoma in situ-like cells (left panel in the figure below). Also called intraepithelial germ cell neoplasia, carcinoma in situ is encountered clinically in subfertile/infertile humans. Occurrence of this condition also has been documented in deer and horses (middle and right panels, respectively).

In situ image

Another facet of this laboratory's activities is the development of a non-mammalian species, Xenopus laevis, as an animal model for comparative reproductive toxicology. Several procedures have been optimized for this species and a possible link between environmental pollutants and the reported declines in amphibian populations is being investigated. This latter phenomenon may very well be an ecological harbinger for deteriorating trends observed in human reproductive health.

Invited presentations:

Veeramachaneni DNR. 2012. Reproductive Toxicology and Environment. Symposium Organizer and Chair, 17th International Congress on Animal Reproduction, Vancouver, British Columbia, Canada.

Veeramachaneni DNR. 2011. Ultrastructural Evaluation of Semen to Assess Effects of Exposure to Environmental Toxicants (in Symposium: Ultrastructural Analysis and Toxicologic Pathology). Society of Toxicologic Pathology, Denver, CO.

Veeramachaneni DNR. 2010. Animal Models of Testicular Germ Cell Cancer. VII Copenhagen Workshop on CIS Testis and Germ Cell Cancer, Rigshopitalet, Copenhagen, Denmark.

Veeramachaneni DNR. 2010. Animal Models for Testicular Cancer (in Symposium: Life in the Womb—Fetal Determinants of Men’s Reproductive Health). American Society of Andrology, Houston, TX.

Veeramachaneni DNR. 2006. Toxicology as a Tool to Unravel "Idiopathic" Reproductive Failure in the Male. Dept of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Uppsala, Sweden.

Veeramachaneni DNR. 2005. Testicular Tumors and Chemical-induced Germ Cell Atypia in Animals. Copenhagen Workshop on Environment, Reproductive Health and Fertility, Rigshospitalet, Copenhagen, Denmark.

Veeramachaneni DNR. 2004. Effects of Endocrine Disrupting Chemicals on Reproductive Behaviour: Laboratory evidence for sexual dysfunction and germ cell atypia. Credo/Comprendo Workshop on the Ecological Relevance of Chemically Induced Endocrine Disruption in Wildlife, University of Exeter, Exeter, UK.

Veeramachaneni DNR. 2003. Relevant Animal Models, Vulnerable Windows, and Late Effects in Mammalian Reproductive Toxicology. Reproductive Toxicology and Chemicals: A Matter of Timing? European Environment Agency and ReproSafe, Swedish EPA, Copenhagen.

Veeramachaneni DNR. 2000. Deteriorating Trends in Male Reproduction: Idiopathic or Environmental? Plenary Lecture, 14th International Congress on Animal Reproduction, Stockholm, Sweden.